Life Extension Magazine
Major Advance for Anti-Aging
When old cells become dysfunctional, they’re supposed to die off through a normal process called apoptosis. But as we age, we accumulate too many of these malfunctioning (senescent) cells that refuse to die.
Sometimes referred to as “zombie cells,” they pump out toxic compounds that degrade nearby cells and incite chronic inflammation that inflicts systemic damage. Compounds called senolytics remove senescent cells. Preclinical studies show that they can slow or reverse certain aspects of aging.
Nutrients like quercetin and theaflavins (from black tea) have demonstrated senolytic activities and have been widely used in recent years. The plant flavonoid fisetin is currently considered one of the most powerful natural senolytics. Its effects are dramatic. Elderly mice given fisetin had their lifespans extended by nearly 10%. This may be analogous to a 75-year-old human living about 7.5 years longer.
The challenge up until now was that fisetin is converted into other compounds in the digestive tract. This means very little whole, unaltered fisetin is absorbed into the bloodstream. Scientists have developed a method to increase fisetin blood levels up to 25 times higher, thus enabling fisetin to be distributed throughout the body.
Enlightened individuals today are taking this highly absorbable fisetin by itself and/or combining it with a once-weekly high potency quercetin + theaflavins for enhanced senolytic effects.
Senescent Cells and Aging
In youth, cells naturally eliminate themselves if they become damaged or dysfunctional. This process is called apoptosis. With age, however, we accumulate more senescent cells that emit toxic byproducts, that cause more cells to become senescent. These dysfunctional cells no longer perform basic functions. They instead inflict localized and systemic damage to our healthy cells.
Senescent cells undergo a series of transformations that result in their secreting high levels of toxic compounds, collectively referred to as SASP or senescence-associated secretory phenotype.
As a result, the buildup of senescent cells has been shown to accelerate the aging process and increase the risk of age-related diseases, including:
- Vision loss,
- Neurodegenerative disorders,
- Emphysema, and
Research shows that just one senescent cell out of 7,000-15,000 healthy cells can initiate degenerative aging. Removing senescent cells from the body can reduce the cellular drivers of aging and improve overall health. That’s where senolytics come in.
Senolytics to the Rescue
Senolytics are compounds that enable the body to remove senescent cells. They work by reactivating the apoptosis switch in senescent cells. That causes these toxic cells to die and make room for healthy young cells.
Published scientific studies demonstrate that removing senescent cells from the body improves markers of aging and prolongs lifespan in some models. In mice with atherosclerosis, removing senescent cells significantly inhibited the growth of arterial plaque and even caused it to regress. This could be an important step in preventing heart and blood vessel disease.
In another study, a mouse model of aging showed that removing senescent cells benefited multiple tissues, while delaying the onset and slowing the progression of age-related disorders.
Fisetin: Today’s Ultimate Senolytic
Scientists have studied many different nutrients, searching for effective senolytics.
Fisetin is the most potent “on target” senolytic known today.
Fisetin is a flavonoid found in small amounts in strawberries, apples, persimmons, grapes, onions, and other plants. A cell study found that it eliminated about 70% of senescent cells – while doing no harm to healthy human cells. These and other effects of fisetin have been shown to increase longevity in various animal models. Mice given fisetin lived an average of about 2.5 months longer, an almost 10% extension of lifespan – even when treatment started at the human equivalent of 75 years of age.
Other Benefits of Fisetin
The effects of fisetin go beyond its potent senolytic activity.
- Protects the brain in various models of neurodegenerative disorders,
- Improves outcomes in people who have suffered strokes,
- Helps prevent malignant changes inside cells,
- In animal and experimental models, helps fight obesity and type II diabetes tendencies,
- Reduces the risk of atrial fibrillation after a heart attack, in an animal study,
- Reduces levels of pro-inflammatory mediators, in a study of colorectal patients, and
- Based on results of preclinical studies, may inhibit cancer migration and growth and incite cancer cell death.
Fisetin also has an ability to impact many of the same cellular pathways that calorie restriction does. Reducing food intake through a calorie-restricted diet has been shown to slow aging, extend lifespan, and improve resistance to disease.
WHAT YOU NEED TO KNOW
Removing Senescent Cells for Better Health
- With age, we accumulate senescent cells, dysfunctional cells that refuse to die off. These cells are associated with accelerated aging and age-related disease.
- Senolytics are compounds that can remove senescent cells, helping to maintain optimal function and youthful health. In preclinical studies, senolytics slow or even reverse aging.
- The compound fisetin is one of the most potent plant-derived senolytics ever discovered. In animal research, it effectively removes senescent cells and boosts longevity. Old mice given fisetin had their lifespans extended by nearly 10%.
- Quercetin is another plant compound that has significant senolytic effects and improves markers of health. It is even more powerful when enhanced with senolytic black tea compounds called theaflavins.
- Fisetin, quercetin, theaflavins, and apigenin are nutrients with senolytic activity.
Until recently, there’s been a challenge with oral fisetin: It is rapidly converted into other compounds in the gut. Scientists have solved this problem by combining fisetin with a fiber called galactomannans, isolated from the spice fenugreek.
This formulation has been shown to increase the bioavailability (absorption) of fisetin by as much as 25 times, greatly enhancing its impact.
The Power of Quercetin
Before fisetin, quercetin, found in many fruits and vegetables, was one of the first plant-derived flavonoids to be tested as a senolytic. Quercetin has long been recognized for a range of benefits, including:
- Anti-inflammatory activity, shown to protect cells and tissues from injury,
- Improved markers of aging and extended lifespan in lab studies, and
- Reduction or prevention of age-related disease and dysfunction in human studies.
The medical literature supporting the senolytic effects of quercetin has been growing over many years. In a study published in late 2019, quercetin successfully removed senescent cells in the kidneys of mice. This improved function and decreased the fibrosis (scarring) that leads to kidney failure.
Quercetin can be difficult to absorb. Scientists got around this problem by combining it with a type of fatty substance called a phospholipid. The phospholipid serves as a carrier, allowing much more quercetin to enter the bloodstream and exert its effects throughout the body.
INTERMITTENT OR CONTINUAL THERAPY: WHICH SENOLYTIC PROGRAM IS MOST EFFECTIVE?
There’s a great deal of debate in the longevity community about the ideal treatment regimen for senolytic therapies.
For now, intermittent therapy appears to be the best approach to reducing senescent cells. Drugs that reduce expression of pro-inflammatory compounds secreted by senescent cells, for example, seem more effective when taken on an intermittent basis.
Based upon the available preclinical research, once-weekly ingestion of high doses of fisetin, quercetin, theaflavins, and apigenin appears to be the optimal senolytic approach.
Boosting Quercetin’s Effects
Research has shown that quercetin works even more effectively when coupled with a chemotherapy drug, dasatinib.
When this combination was administered to old mice, its ability to eliminate senescent cells led to improvements in grip strength, coat condition, movement, and overall health. The first human study of this combination was published in 2019. Patients with idiopathic pulmonary fibrosis (a progressive lung disease) were given 100 mg/day dasatinib and 1,250 mg/day quercetin on three consecutive days per week for three weeks.
This improved several measurements of physical activity, including distance walked and walking speed. Scientists set out to identify a compound that would enhance quercetin senolytic effects by the same mechanisms as dasatinib, but without the side effects of a cancer drug.
The most effective candidate they found was a group of compounds in black tea called theaflavins. In a similar way to dasatinib, theaflavins block an anti-apoptotic protein called BCL-2. If you wonder what BCL stands for, it is “B-cell lymphoma.” A compound that blocks BCL-2 might reduce risk of this common malignancy.
In a mouse study, theaflavins demonstrated significant senolytic effects.
Targeting Toxic Secretions Emitted by Senescent Cells
Apigenin is a flavonoid found in certain herbs, fruits, and vegetables. In two recent studies, apigenin was found to inhibit the SASP, also known as the senescence-associated secretory phenotype. This resulted in a reduction of pro-inflammatory compounds produced by senescent cells.
Reducing inflammation caused by the SASP while diminishing the senescent cell burden gives a two-pronged strategy for fighting this enemy of longevity. Quercetin and theaflavins (from black tea) function via separate and complementary mechanisms to purge the body of senescent cells. Fisetin, a strawberry flavonoid, has been shown to be the most effective senolytic when compared to a panel of flavonoids, removing aged, dysfunctional senescent cells in preclinical studies.
A multi-targeted approach utilizing highly absorbable quercetin and fisetin, plus theaflavins, and apigenin, can attack cellular senescence from multiple angles, helping to rid the body of the damage it causes.
Old or dysfunctional cells promote chronic inflammation and contribute to loss of function and increased risk for age-related disease. Senolytics can cleanse the body of these cells, improving organ function and preventing disease.
A plant extract called fisetin has been identified as the most powerful senolytic known so far. An innovative formulation has enhanced fisetins absorption up to 25 times. Fisetin by itself or combined with other known senolytic ingredients such as quercetin and theaflavins, may provide superior senolytic benefits.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at (0011) 1-866-864-3027.